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Creation of "disease metallomics" to understand the relationship between fluctuations of heavy metals/trace elements and diseases

Research Project

Project/Area Number 21K19321
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionTohoku University

Principal Investigator

Saito Yoshiro  東北大学, 薬学研究科, 教授 (70357060)

Co-Investigator(Kenkyū-buntansha) 外山 喬士  東北大学, 薬学研究科, 講師 (50720918)
Project Period (FY) 2021-07-09 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2022: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsメタロミクス / セレン / 生活習慣病 / がん / 亜鉛 / メチル水銀 / 水銀 / 糖尿病 / ICP-MS / 鉄 / セレノプロテインP / コホート研究
Outline of Research at the Start

本研究の目的は、網羅的な重金属・微量元素解析“メタロミクス”を駆使し、重金属・微量元素の多様な変化と生活習慣病や炎症性疾患との関連性を理解する「疾患メタロミクス」を確立することである。応募者の研究から、必須微量元素セレン(Se)を含む血漿タンパク質セレノプロテインP(SeP)が、2型糖尿病患者で増加し、増加したSePが糖代謝を悪化する“悪玉”として作用することが明らかとなった。本研究では、SePが増加する2型糖尿病やがん、SePが低下する炎症性疾患モデルについてメタロミクス解析を行い、重金属・微量元素の変化と病態との関連性を明らかにする。

Outline of Final Research Achievements

The purpose of this study is to investigate the relationship between changes in heavy metals and several diseases by using comprehensive heavy metal and trace element analysis "metallomics." From the metallomics analysis of biological samples from diseased patients and model animals, several trace metals show significant differences. We established a new analysis method that integrates all the measured elements and clusters them by the UMAP method. We found the clustering of trace element profiles in brain cancers, such as glioblastoma. We further apply this novel analytical method to several diseases and animal models to develop a molecular pathology based on the understanding of various changes in heavy metals and trace elements.

Academic Significance and Societal Importance of the Research Achievements

ICP-MSの高感度化および高精度化が進み、網羅的な微量金属解析“メタロミクス”が開発されてきた。本研究では、メタロミクスを疾患患者検体に適応し、網羅的解析から単一元素の変化を抽出するとともに、得られた測定値を統合し、全体の変化として比較する手法を開発した。本研究より、生体機能の変化を元素全体の変化から捉える新たな手法が開発された。本研究を軸に、疾患を微量元素の変動から理解する新たな学術大系「疾患メタロミクス」を確立する。

Report

(2 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (25 results)

All 2022 2021 Other

All Int'l Joint Research (4 results) Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (5 results) (of which Invited: 5 results) Book (1 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] University of Copenhagen(デンマーク)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of Modena and Reggio Emilia(イタリア)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] Heinrich-Heine-University(ドイツ)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] National Institute of Oncology(ハンガリー)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Selenoprotein P-mediated reductive stress impairs cold-induced thermogenesis in brown fat2022

    • Author(s)
      Oo Swe Mar、Oo Hein Ko、Takayama Hiroaki、Ishii Kiyo-aki、Takeshita Yumie、Goto Hisanori、Nakano Yujiro、Kohno Susumu、Takahashi Chiaki、Nakamura Hiroyuki、Saito Yoshiro、Matsushita Mami、Okamatsu-Ogura Yuko、Saito Masayuki、Takamura Toshinari
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 13 Pages: 110566-110566

    • DOI

      10.1016/j.celrep.2022.110566

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Nephronectin influences EAE development by regulating the Th17/Treg balance via reactive oxygen species2022

    • Author(s)
      Honda M, Segawa T, Ishikawa K, Maeda M, Saito Y, Kon S.
    • Journal Title

      Am J Physiol Cell Physiol .

      Volume: 322(4) Issue: 4 Pages: C699-C711

    • DOI

      10.1152/ajpcell.00376.2021

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Safety of selenium exposure and limitations of selenoprotein maximization: Molecular and epidemiologic perspectives2022

    • Author(s)
      Vinceti Marco、Filippini Tommaso、Jablonska Ewa、Saito Yoshiro、Wise Lauren A.
    • Journal Title

      Environmental Research

      Volume: 211 Pages: 113092-113092

    • DOI

      10.1016/j.envres.2022.113092

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of selenoprotein P expression in the function of pancreatic β cells: Prevention of ferroptosis-like cell death and stress-induced nascent granule degradation2022

    • Author(s)
      Kitabayashi Nanako、Nakao Shohei、Mita Yuichiro、Arisawa Kotoko、Hoshi Takayuki、Toyama Takashi、Ishii Kiyo-aki、Takamura Toshinari、Noguchi Noriko、Saito Yoshiro
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 183 Pages: 89-103

    • DOI

      10.1016/j.freeradbiomed.2022.03.009

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipid peroxidation products as a mediator of toxicity and adaptive response-The regulatory role of selenoprotein and vitamin E2021

    • Author(s)
      Saito Yoshiro
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 703 Pages: 108840-108840

    • DOI

      10.1016/j.abb.2021.108840

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Methylmercury induces neuronal cell death by inducing TNF-α expression through the ASK1/p38 signaling pathway in microglia2021

    • Author(s)
      Toyama Takashi、Hoshi Takayuki、Noguchi Takuya、Saito Yoshiro、Matsuzawa Atsushi、Naganuma Akira、Hwang Gi-Wook
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 9831-9831

    • DOI

      10.1038/s41598-021-89210-7

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selenium Transport Mechanism via Selenoprotein P?Its Physiological Role and Related Diseases2021

    • Author(s)
      Saito Yoshiro
    • Journal Title

      Frontiers in Nutrition

      Volume: 8 Pages: 685517-685517

    • DOI

      10.3389/fnut.2021.685517

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a novel endogenous long non-coding RNA that inhibits selenoprotein P translation2021

    • Author(s)
      Mita Yuichiro、Uchida Risa、Yasuhara Sayuri、Kishi Kohei、Hoshi Takayuki、Matsuo Yoshitaka、Yokooji Tadashi、Shirakawa Yoshino、Toyama Takashi、Urano Yasuomi、Inada Toshifumi、Noguchi Noriko、Saito Yoshiro
    • Journal Title

      Nucleic Acids Research

      Volume: 49 Issue: 12 Pages: 6893-6907

    • DOI

      10.1093/nar/gkab498

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diverse cytoprotective actions of vitamin E isoforms- role as peroxyl radical scavengers and complementary functions with selenoproteins2021

    • Author(s)
      Saito Yoshiro
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 175 Pages: 121-129

    • DOI

      10.1016/j.freeradbiomed.2021.08.234

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] 必須微量元素セレンと超硫黄分子による生体防御とレドックス―カルコゲンによるシグナルネットワーク2022

    • Author(s)
      斎藤芳郎
    • Organizer
      第2回 レドックスR&D戦略委員会 春のシンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] セレノプロテインPの抗酸化機能と疾患-その発現と細胞内抗酸化システムの変化2021

    • Author(s)
      斎藤芳郎
    • Organizer
      第74回日本酸化ストレス学会/第21回日本NO学会 合同学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] セレノプロテインと抗加齢医学-糖尿病とレドックス制御2021

    • Author(s)
      斎藤芳郎
    • Organizer
      第21回日本抗加齢医学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 膵β細胞のインスリン分泌におけるセレノプロテインの機能-リソソーム活性の制御2021

    • Author(s)
      斎藤芳郎
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 必須微量元素セレンを含むアミノ酸の代謝と疾患-新たな輸送経路と生体内レドックス制御2021

    • Author(s)
      斎藤芳郎
    • Organizer
      第11回 新アミノ酸分析研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Book] セレンによる超硫黄分子ターンオーバー2021

    • Author(s)
      外山喬士、斎藤芳郎
    • Total Pages
      6
    • Publisher
      生化学
    • Related Report
      2021 Research-status Report
  • [Remarks] 2021年6月18日 プレスリリース「糖尿病を予防する新規RNAを発見」

    • URL

      https://www.tohoku.ac.jp/japanese/2021/06/press20210618-00-rna.html

    • Related Report
      2021 Research-status Report
  • [Remarks] 2022年3月4日 第2回レドックスR&D戦略委員会 春のシンポジウム主催

    • URL

      http://www.med.hirosaki-u.ac.jp/~admed/redox/symposium2022.html

    • Related Report
      2021 Research-status Report
  • [Remarks] 2022年3月23日 プレスリリース「インスリン分泌に必要なセレンの働きを解明 」

    • URL

      https://www.tohoku.ac.jp/japanese/2022/03/press20220323-04-sep.html

    • Related Report
      2021 Research-status Report
  • [Remarks] 東北大学大学院薬学研究科 代謝制御薬学分野

    • URL

      http://www.pharm.tohoku.ac.jp/~taisya/index.html

    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] グリオブラストーマの治療薬のスクリーニング方法、治療薬、予後判定方法2021

    • Inventor(s)
      斎藤芳郎、外山喬士、杉浦ひかり
    • Industrial Property Rights Holder
      斎藤芳郎、外山喬士、杉浦ひかり
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] COVID-19治療剤2021

    • Inventor(s)
      斎藤芳郎、外山喬士ら
    • Industrial Property Rights Holder
      斎藤芳郎、外山喬士ら
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Research-status Report
    • Overseas

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Published: 2021-07-13   Modified: 2024-12-25  

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